Durán-Lara Esteban F, Marple Jennifer L, Giesen Joseph A, Fang Yunlan, Jordan Jacobs H, Godbey W Terrence, Marican Adolfo, Santos Leonardo S, Grayson Scott M
Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources; Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation - Center for Systems Biotechnology, FCR-CSB, Talca University , P.O. Box 747, Talca, Chile.
Biomacromolecules. 2015 Nov 9;16(11):3434-44. doi: 10.1021/acs.biomac.5b00657. Epub 2015 Oct 21.
Lysine-containing polymers have seen broad application due to their amines' inherent ability to bind to a range of biologically relevant molecules. The synthesis of multiple generations of polyester dendrimers bearing lysine groups on their periphery is described in this report. Their hydrolytic stabilities with respect to pH and time, their toxicity to a range of cell lines, and their possible application as nano-detoxification agents of organophosphate compounds are all investigated. These zeroth-, first-, and second-generation water-soluble dendrimers have been designed to bear exactly 4, 8, and 16 lysine groups, respectively, on their dendritic periphery. Such monodisperse bioactive polymers show potential for a range of applications including drug delivery, gene delivery, heavy metal binding, and the sequestration of organic toxins. These monodisperse bioactive dendrimers were synthesized using an aliphatic ester dendritic core (prepared from pentaerythritol) and protected amino acid moieties. This library of lysine-conjugated dendrimers showed the ability to efficiently capture the pesticide dichlorvos, confirming the potential of dendrimer-based antidotes to maintain acetylcholinesterase activity in response to poisoning events.
含赖氨酸的聚合物因其胺基具有与一系列生物相关分子结合的固有能力而得到广泛应用。本报告描述了在其外围带有赖氨酸基团的多代聚酯树枝状大分子的合成。研究了它们在不同pH值和时间下的水解稳定性、对一系列细胞系的毒性以及它们作为有机磷化合物纳米解毒剂的可能应用。这些第零代、第一代和第二代水溶性树枝状大分子在其树枝状外围分别设计为恰好带有4个、8个和16个赖氨酸基团。这种单分散生物活性聚合物在包括药物递送、基因递送、重金属结合和有机毒素螯合在内的一系列应用中显示出潜力。这些单分散生物活性树枝状大分子是使用脂肪族酯树枝状核心（由季戊四醇制备）和受保护的氨基酸部分合成的。这个赖氨酸共轭树枝状大分子文库显示出有效捕获农药敌敌畏的能力，证实了基于树枝状大分子的解毒剂在中毒事件中维持乙酰胆碱酯酶活性的潜力。
